title: Bone augmentation for cancellous bone- development of a new animal model.
abstract: BACKGROUND
  Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep.
  
  
  METHODS
  The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (Ø 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation.
  
  
  RESULTS
  The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples.
  
  
  CONCLUSIONS
  This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty.
authors.affiliation: Musculoskeletal Research Unit (MSRU), Equine Department, University of Zurich, Winterthurerstrasse 260, Zurich CH-8057, Switzerland. kklein@vetclinics.uzh.ch
authors.forename: Karina
authors.initials: K
authors.lastname: Klein
authors.forename: Enrico
authors.initials: E
authors.lastname: Zamparo
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kronen
authors.forename: Katharina
authors.initials: K
authors.lastname: Kämpf
authors.forename: Mariano
authors.initials: M
authors.lastname: Makara
authors.forename: Thomas
authors.initials: T
authors.lastname: Steffen
authors.forename: Brigitte
authors.initials: B
authors.lastname: von Rechenberg
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D018786:Bone Substitutes / Q000494:pharmacology*; D016025:Bone Transplantation; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D015203:Reproducibility of Results; D012756:Sheep / Q000502:physiology*; D013977:Tibia / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D014182:Transplantation, Autologous; D054854:Vertebroplasty / Q000295:instrumentation* / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes